1. Field of the Invention
The present invention relates to a diagnostic nuclear medicine. More specifically, the present invention relates to tumor imaging utilizing radioactive gallium.
2. Description of the Prior Art
Gallium-67, as the carrier-free citrate, is used routinely in clinical medicine in the diagnosis, staging and monitoring of several neoplastic disease states (Semin Nucl Med 6: 331-334, 1976). Unfortunately, this agent is plagued with imaging problems which are related to plasma protein binding. Specifically, gallium has an affinity for blood and soft tissue proteins, and when given in very low doses, is extensively bound (J Pharmacol Exp Therapeut 168: 193-198, 1973). Gallium also has an affinity for tumors (Science 167:289-290, 1970; J Nucl Med 10: 103-105, 1969) and abscesses (J Nucl Med 21: 484-488, 1980). After intravenous administration, gallium activity in tumors is seen immediately and reaches a maximum within eighteen hours (Semin Nucl Med 8: 193-203, 1978). Biologic clearing of gallium from blood and soft tissue binding sites is a slow process, and results in the presence of image obscuring activity long after the ideal imaging time. Three major consequences of this binding phenomenon are: (a) it is necessary to delay imaging procedures for long periods of time (48-72 hours) to allow for the clearance of non-productive radioactivity; (b) the long waiting period allows the build-up of image obscuring activity in the intestinal tract due to secretion of gallium into the large bowel (J Nucl Med 14: 208-214, 1973); and (c) prolonged retention of large quantities of .sup.67 Ga in the body results in a relatively high radiation dose (J Nucl Med 12: 755-756, 1973).
Several reports have described methods or agents which attempt to enhance the process of imaging a tumor or abscess by shortening the biologic half life of carrier-free gallium-67 citrate. Generally, these fall into two categories: (a) agents which compete with radioactive gallium for blood and tissue binding sites, thus releasing the radioactive metal ion making it available for kidney elimination; or (b) complexing or chelating agents which compete with blood and tissue binding sites for free gallium, forming a complex which is rapidly cleared by the kidney.
The initial work took the first approach and used a group (IIB) metal complex (Scandium citrate) as a selective competitive binding agent (South Med J 66: 1339-1340, 1973; J Nucl Med 21: 361-365, 1980). Scandium, by occupying gallium binding sites on blood proteins, prevents the accumulation of gallium on these sites. Scandium appears to have little or no effect upon gallium binding in tumors. When used in animal studies, where gallium-67 and scandium citrates were injected simultaneously, extremely high tumor to blood and tumor to tissue ratios were obtained. Unfortunately, scandium produces a severe hemolytic anemia when administered to man (South Med J 66: 1339-1340, 1973; J Nucl Med 21: 361-365, 1980). The use of iron dextran in similar fashion to clear gallium from rabbits bearing induced abscesses resulted in the clearing of gallium with enhanced abscess uptake of gallium (J Nucl Med 17: 356-358, 1976). This ion, however, has no clinical application due to the large dose of iron required (J Nucl Med 21: 421-424, 1980). More recently, it has been shown that relatively large doses of non-radioactive gallium will decrease blood activity without significantly reducing tumor activity (J Nucl Med 20: 656, 1979; Invest Radiol 14: 482-492, 1979).
Several investigators have used the second approach, employing a chelating agent, desferoxamine, to reduce gallium blood activity (J Nucl Med 21: 421-425, 1980; J Nucl Med 20: 248-251, 1979; Radiology 131: 775-779, 1979; Radiology 130: 241-244, 1979). The resulting gallium desferoxamine complex is eliminated via the kidney at a rate greater than that observed for gallium alone. Unfortunately, this clearing agent must be administered 24 hours after the gallium injection in order to minimize loss of tumor activity.